OBJECTIVES: The purpose of this study was to test the hypothesis, with noninvasive multimodality imaging, that allogeneic mesenchymal stem cells (MSCs) produce and/or stimulate active cardiac regeneration in vivo after myocardial infarction (MI).
BACKGROUND: Although intramyocardial injection of allogeneic MSCs improves global cardiac function after MI, the mechanism(s) underlying this phenomenon are incompletely understood.
METHODS: We employed magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) imaging in MSC-treated pigs (n = 10) and control subjects (n = 12) serially for a 2-month period after anterior MI. A sub-endocardial rim of tissue, demonstrated with MDCT, was assessed for regional contraction with MRI tagging. Rim thickness was also measured on gross pathological specimens, to confirm the findings of the MDCT imaging, and the size of cardiomyocytes was measured in the sub-endocardial rim and the non-infarct zone.
RESULTS: Multi-detector computed tomography demonstrated increasing thickness of sub-endocardial viable myocardium in the infarct zone in MSC-treated animals (1.0 ± 0.2 mm to 2.0 ± 0.3 mm, 1 and 8 weeks after MI, respectively, p = 0.028, n = 4) and a corresponding reduction in infarct scar (5.1 ± 0.5 mm to 3.6 ± 0.2 mm, p = 0.044). No changes occurred in control subjects (n = 4). Tagging MRI demonstrated time-dependent recovery of active contractility paralleling new tissue appearance. This rim was composed of morphologically normal cardiomyocytes, which were smaller in MSC-treated versus control subjects (11.6 ± 0.2 µm vs. 12.6 ± 0.2 µm, p < 0.05).
CONCLUSIONS: With serially obtained MRI and MDCT, we demonstrate in vivo reappearance of myocardial tissue in the MI zone accompanied by time-dependent restoration of contractile function. These data are consistent with a regenerative process, highlight the value of noninvasive multimodality imaging to assess the structural and functional basis for myocardial regenerative strategies, and have potential clinical applications.
Journal of the American College of Cardiology, 2006. 48(10): p. 2116-2124.
10.1016/j.jacc.2006.06.073.
http://content.onlinejacc.org/cgi/content/full/48/10/2116

Aims: We sought to determine whether intra-aortic balloon pump (IABP) counterpulsation improves the recovery of left ventricular (LV) systolic function after reperfused acute myocardial infarction (AMI).
Methods and results: Fourteen dogs underwent 90‐min coronary artery occlusion followed by reperfusion. Seven animals were randomized to IABP counterpulsation immediately after reperfusion. Tagged, cine, and contrast-enhanced magnetic resonance imaging were used for regional and global LV functional assessment and MI characterization, respectively. Image acquisition was performed at 1 h, 6 h, and 24 h after reperfusion, during which the IABP device was paused.
Animals randomized to IABP demonstrated an earlier improvement of LV ejection fraction when compared with controls (25±3 vs. 25±2% at 1 h, P=0.91; 36±3 vs. 26±2% at 6 h, P=0.015; and 38±3 vs. 35±1% at 24 h, P=0.34). Regional functional analyses revealed the same behaviour among non-infarcted risk regions, i.e., earlier circumferential systolic strain improvement in the IABP group than in controls (−5.4±0.4 vs. −5.3±0.5% at 1 h, P=0.86; −12.1±1.0 vs. −6.0±0.4% at 6 h, P Conclusion: IABP counterpulsation accelerates but does not significantly improve the recovery of LV systolic function after reperfused AMI.
European Heart Journal, 2005. 26(12): p. 1235-1241.
10.1093/eurheartj/ehi137.
http://eurheartj.oxfordjournals.org/content/26/12/1235.full

Aims: This study was designed to characterise both the systolic and diastolic mechanical properties of regions with different degrees of myocardial ischaemic injury after reperfused acute myocardial infarction (AMI).
Methods and Results: Fourteen dogs underwent 90-min coronary artery occlusion followed by reperfusion. Image acquisition was performed 24 h after reperfusion using three techniques: tagged, first-pass perfusion and delayed-enhancement magnetic resonance imaging (MRI). Systolic circumferential strain and both systolic and diastolic strain rates were calculated in 30 segments/animal. Transmural AMI segments displayed reduced systolic contractility when compared to subendocardial AMI segments (systolic strain=–2.5±0.5% versus –6.0±0.9%, P Conclusion: Reversibly injured regions can demonstrate persistent diastolic dysfunction despite complete systolic functional recovery after reperfused AMI. Moreover, the presence of no-reflow entails profound systolic and diastolic dysfunction. Finally, tagged magnetic resonance imaging (MRI) strain rate analysis provides detailed mechanical characterisation of regions with different degrees of myocardial ischaemic injury.
European Heart Journal, 2004. 25(16): p. 1419-1427.
10.1016/j.ehj.2004.06.024.
http://eurheartj.oxfordjournals.org/content/25/16/1419.full

Background: In compensated aortic stenosis (AS), cardiac performance measured at the ventricular chamber is typically supranormal, whereas measurements at the myocardium are often impaired. We investigated intramyocardial mechanics after aortic valve replacement (AVR) and the effects relative to the presence or absence of coronary artery disease (CAD+ or CAD–), respectively.
Methods and Results: Twenty-nine patients (46 to 91years, 10 female) with late but not decompensated AS inderwent cardiovascular MRI before AVR (PRE), with follow-up at 6±1 (EARLY) and 13±2 months (LATE) to determine radiofrequency tissue-tagged left ventricle (LV) transmural circumferential strain, torsion, structure, and function. At the myocardial level, concentric LV hypertrophy regressed 18% LATE (93±22 versus 77±17g/m2; P Conclusions: In AS patients after AVR, reverse remodeling of the supranormal systolic function parallels improvement in cardiovascular MRI-derived regression of LV hypertrophy and LV intramyocardial strain. However, discordant effects are evident after AVR, driven by CAD status, suggesting that the typical AVR benefits are experienced disproportionately by those without CAD and not by those obliged to undergo concomitant coronary artery bypass grafting/AVR.
Circulation, 2005. 112(9_suppl): p. I-429-436.
10.1161/CIRCULATIONAHA.104.525501.
http://circ.ahajournals.org/cgi/content/abstract/circulationaha;112/9_suppl/I-429

Purpose: To retrospectively evaluate with dynamic magnetic resonance (MR) imaging the changes in global and regional left ventricular (LV) function after surgical ventricular restoration (SVR) performed in chronic ischemic heart disease patients with large nonaneurysmal or aneurysmal postmyocardial infarction zones.
Materials and Methods: The study was performed with institutional review board approval, and a waiver of individual informed consent was obtained. The study was HIPAA compliant. Patients (83 men, 22 women; mean age, 61 years ± 9 [standard deviation]) were evaluated with MR imaging before and after SVR as follows: pre-SVR examination (n = 105; 25 days ± 39 before SVR; median, 7 days; range, 1–189 days), early post-SVR examination (n = 95, 7 days ± 3 after SVR), and late post-SVR (n = 35, 313 days ± 158 after SVR). Cine MR imaging allowed calculation of ejection fraction and rate-corrected velocity of circumferential fiber shortening (VcfC) for global LV functional evaluation, whereas tagged MR imaging (spatial modulation of magnetization with harmonic phase analysis) permitted assessment of regional circumferential strain (EC) with coronary distribution. VcfC and EC were computed at both LV base- and mid-LV short-axis levels remote from the site of anteroapical SVR.
Results: Prior to SVR, LV dilatation and diminished global and regional LV function were observed. At early post-SVR examination, VcfC had improved significantly but EC showed a worsening trend overall, although only EC of the right coronary artery at the mid-LV level worsened significantly. At late post-SVR examination, VcfC values were improved when compared with pre-SVR values, although EC showed no statistically significant improvement. When compared with that at early post-SVR examination, however, EC showed significant improvement in two segments: left anterior descending artery and right coronary artery at mid-LV level.
Conclusion: Although volume-based indexes of global LV function improve significantly after SVR, regional LV function did not improve significantly; there was evidence of continued LV remodeling after SVR.
Radiology, 2006. 241(3): p. 710-717.
10.1148/radiol.2413051440.
http://radiology.rsna.org/content/241/3/710.full

Two-dimensional (2-D) strain (ε2-D) on the basis of speckle tracking is a new technique for strain measurement. This study sought to validate ε2-D and tissue velocity imaging (TVI)–based strain (εTVI) with tagged harmonic-phase (HARP) magnetic resonance imaging (MRI). Thirty patients (mean age 62 ± 11 years) with known or suspected ischemic heart disease were evaluated. Wall motion (wall motion score index 1.55 ± 0.46) was assessed by an expert observer. Three apical images were obtained for longitudinal strain (16 segments) and 3 short-axis images for radial and circumferential strain (18 segments). Radial εTVI was obtained in the posterior wall. HARP MRI was used to measure principal strain, expressed as maximal length change in each direction. Values for ε2-D, εTVI, and HARP MRI were comparable for all 3 strain directions and were reduced in dysfunctional segments. The mean difference and correlation between longitudinal ε2-D and HARP MRI (2.1 ± 5.5%, r = 0.51, p <0.001) were similar to those between longitudinal εTVI and HARP MRI (1.1 ± 6.7%, r = 0.40, p <0.001). The mean difference and correlation were more favorable between radial ε2-D and HARP MRI (0.4 ± 10.2%, r = 0.60, p <0.001) than between radial εTVI and HARP MRI (3.4 ± 10.5%, r = 0.47, p <0.001). For circumferential strain, the mean difference and correlation between ε2-D and HARP MRI were 0.7 ± 5.4% and r = 0.51 (p <0.001), respectively.
In conclusion, the modest correlations of echocardiographic and HARP MRI strain reflect the technical challenges of the 2 techniques. Nonetheless, ε2-D provides a reliable tool to quantify regional function, with radial measurements being more accurate and feasible than with TVI. Unlike εTVI, ε2-D provides circumferential measurements.
The American Journal of Cardiology, 2006. 97(11): p. 1661-1666.
10.1016/j.amjcard.2005.12.063.
http://www.ajconline.org/article/S0002-9149(06)00381-X/abstract

Current patient selection criteria for Cardiac Resynchronization Therapy (CRT), an efficacious treatment for heart failure, include no measure of disconjugate cardiac contractility other than prolonged QRS on electrocardiogram. Using cardiac magnetic resonance imaging, we examined the roles of cardiac asymmetry, asynchrony, and circumferential strain in DCC with the principal aim of generating a robust numerical index for use in future trials of CRT. Standard cardiac magnetic resonance imaging was done on a GE 1.5 Tesla Signa LX MRI clinical scanner (GE Healthcare, Milwaukee, WI, USA) and analyzed by MASS Analysis (MEDIS, Leiden, The Netherlands). The methods were evaluated in eleven patients with advanced heart failure due to ischemic and non-ischemic cardiomyopathy, who did not qualify under current criteria for CRT, five CRT candidates pre-op and eleven normal subjects. Using t-test and standardized differences (SD = sd/diff, Power (N) = number of patients to reach p < .05) we determined efficacy. Indices of asymmetry and asynchrony (Ism and Isn, respectively) could be measured with accuracy and provided excellent statistical power when used as surrogate markers to delineate heart failure and CRT patients from control subjects. Asymmetry and asynchrony in heart contraction are both critical components of dilated cardiomyopathy that can be improved by CRT. Magnetic resonance asynchrony is efficacious in screening patients and should now be compared with recently published echocardiography data to improve outcome for this costly but valuable therapy.
Journal of Cardiovascular Magnetic Resonance, 2005. 7(5): p. 827 - 834.
10.1080/10976640500287992
http://informahealthcare.com/doi/abs/10.1080/10976640500287992?journalCode=lcmr

OBJECTIVES: This study sought to determine whether increased carotid intima-media thickness (IMT) is related to reduced regional myocardial function in participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
BACKGROUND: Carotid artery IMT is an established index of subclinical atherosclerosis, and tagged magnetic resonance imaging (MRI) can detect incipient alterations of segmental function that precede overt myocardial failure.
METHODS: The MESA study is a prospective observational study including four ethnic groups free from clinical cardiovascular disease. Peak midwall systolic circumferential strain (ECC) and regional strain rates were calculated by harmonic phase from tagged MRI data of 500 participants. Systolic ECC and diastolic strain rate were regressed on IMT of the common carotid artery defined by ultrasound, with adjustments for body mass index, blood pressure, cholesterol, diabetes, smoking, left ventricular hypertrophy, C-reactive protein, age, and gender.
RESULTS: The mean participant age was 66 ± 10 years (mean ± SD). Among the 58 participants, 4% were male and the interquartile (25th to 75th percentile) range for IMT was 0.25 mm. Multiple linear regression analyses showed that increased IMT was related to reduced systolic regional function (less shortening ECC) in all myocardial regions (p < 0.05), except in the inferior wall. The analyses also showed that greater IMT was associated with a lower diastolic strain rate (diastolic reduced function) in all regions (p < 0.01), except in the anterior wall.
CONCLUSIONS: Greater carotid IMT is associated with alterations of myocardial strain parameters reflecting reduced systolic and diastolic myocardial function. These observations indicate a relationship between subclinical atherosclerosis and incipient myocardial dysfunction in a population free of clinical heart disease.
Journal of the American College of Cardiology, 2006. 47(12): p. 2420-2428.
10.1016/j.jacc.2005.12.075.
http://content.onlinejacc.org/cgi/content/full/47/12/2420

Purpose: To prospectively determine whether mechanical behavior of left ventricular wall segments that contain different degrees of scar tissue and are located at different distances from the interface between infarcted and noninfarcted myocardial tissue can help predict inducibility of monomorphic ventricular tachycardia (VT) in patients with ischemic cardiomyopathy.
Materials and Methods: This HIPAA-compliant study was institutional review board approved; written informed consent was obtained from all patients. Forty-six patients (36 men, 10 women; mean age ± standard deviation, 61.6 years ± 11.9) with prior myocardial infarction (MI) and left ventricular dysfunction were referred for defibrillator implantation and underwent an electrophysiologic examination and tagged contrast-enhanced magnetic resonance (MR) imaging. Peak circumferential shortening strain (Ecc) and time to peak Ecc were measured in 12 segments from short-axis sections. Remote, adjacent, and border zones were defined according to increasing proximity to the MI. Patients in whom monomorphic VT could be induced (ie, inducible patients) were considered positive for inducibility. Relationships between inducibility of monomorphic VT, peak Ecc, and time to peak Ecc were analyzed with one-way analysis of variance and Bonferroni test.
Results: Inducible patients had more infarcted and border zone sectors and a shorter time to peak Ecc than did noninducible patients in the border zone and adjacent and infarcted regions (P < .001). Peak Ecc in the border zone of inducible patients (−11.42% ± 0.46 [standard error]) was greater than that in noninducible patients (−10.18% ± 0.38; P < .05). Ratio of Ecc in border zone and in remote regions was greater (P < .05) in inducible patients than in noninducible patients (1.31 ± 0.27 vs 0.64 ± 0.13, respectively).
Conclusion: Enhanced border zone function defined as greater Ecc and earlier time to peak Ecc showed positive correlation to VT inducibility in patients with prior MI and left ventricular dysfunction.
Radiology, 2007. 245(3): p. 712-719.
10.1148/radiol.2452061615.
http://radiology.rsna.org/content/245/3/712.abstract

Background: Left ventricular (LV) torsion is due to oppositely directed apical and basal rotation and has been proposed as a sensitive marker of LV function. In the present study, we introduce and validate speckle tracking echocardiography (STE) as a method for assessment of LV rotation and torsion.
Methods and Results: Apical and basal rotation by STE was measured from short-axis images by automatic frame-to-frame tracking of gray-scale speckle patterns. Rotation was calculated as the average angular displacement of 9 regions relative to the center of a best-fit circle through the same regions. As reference methods we used sonomicrometry in anesthetized dogs during baseline, dobutamine infusion, and apical ischemia, and magnetic resonance imaging (MRI) tagging in healthy humans. In dogs, the mean peak apical rotation was –3.7±1.2° (±SD) and –4.1±1.2°, and basal rotation was 1.9±1.5° and 2.0±1.2° by sonomicrometry and STE, respectively. Rotations by both methods increased (P<0.001) during dobutamine infusion. Apical rotation by both methods decreased during left anterior descending coronary artery occlusion (P<0.007), whereas basal rotation was unchanged. In healthy humans, apical rotation was –11.6±3.8° and –10.9±3.3°, and basal rotation was 4.8±1.7° and 4.6±1.3° by MRI tagging and STE, respectively. Torsion measurement by STE showed good correlation and agreement with sonomicrometry (r=0.94, P<0.001) and MRI (r=0.85, P<0.001).
Conclusions: The present study demonstrates that regional LV rotation and torsion can be measured accurately by STE, suggesting a new echocardiographic approach for quantification of LV systolic function.
Circulation, 2005. 112(20): p. 3149-3156.
10.1161/CIRCULATIONAHA.104.531558.
http://circ.ahajournals.org/cgi/content/short/112/20/3149

Background: The efficacy of cardiac resynchronization therapy (CRT) depends on placement of the left ventricular lead within the late-activated territory. The geographic extent and 3-dimensional distribution of left ventricular (LV) locations yielding optimal CRT remain unknown.
Methods and Results: Normal or tachypacing-induced failing canine hearts made dyssynchronous by right ventricular free wall pacing or chronic left bundle-branch ablation were acutely instrumented with a nonconstraining epicardial elastic sock containing 128 electrodes interfaced with a computer-controlled stimulation/recording system. Biventricular CRT was performed using a fixed right ventricular site and randomly selected LV sites covering the entire free wall. For each LV site, global cardiac function (conductance catheter) and mechanical synchrony (magnetic resonance imaging tagging) were determined to yield 3-dimensional maps reflecting CRT impact. Optimal CRT was achieved from LV lateral wall sites, slightly more anterior than posterior and more apical than basal. LV sites yielding 70% of the maximal dP/dtmax increase covered 43% of the LV free wall. This distribution and size were similar in both normal and failing hearts. The region was similar for various systolic and diastolic parameters and correlated with 3-dimensional maps based on mechanical synchrony from magnetic resonance imaging strain analysis.
Conclusions: In hearts with delayed lateral contraction, optimized CRT is achieved over a fairly broad area of LV lateral wall in both nonfailing and failing hearts, with modest anterior or posterior deviation still capable of providing effective CRT. Sites selected to achieve the most mechanical synchrony are generally similar to those that most improve global function, confirming a key assumption underlying the use of wall motion analysis to optimize CRT.
Circulation, 2007. 115(8): p. 953-961.
10.1161/CIRCULATIONAHA.106.643718.
http://circ.ahajournals.org/cgi/content/short/115/8/953

Purpose: To prospectively investigate the long-term effect of adeno-associated viral (AAV) vector–encoding vascular endothelial growth factor gene (VEGF) (AAV-VEGF) on left ventricular (LV) mass and volumes, as well as on regional contractility and circumferential strain, in a swine model of reperfused myocardial infarction.
Materials and Methods: All experimental procedures received approval from the institutional committee on animal research. Of 16 pigs subjected to reperfused myocardial infarction, six were treated, six were controls, and four died during the ischemic intervention. In six animals, cardiac-specific AAV-VEGF was injected into the periinfarcted and infarcted myocardium 1 hour after reperfusion. Magnetic resonance (MR) imaging was performed at 3 days and 8 weeks after infarction by using cine, tagged, and delayed enhancement (with gadoterate meglumine) sequences to measure global and regional LV function and infarct size. At postmortem examination, tissue samples stained with isolectin B4, Masson trichrome, and hematoxylin-eosin were used to characterize injured myocardium. Two-tailed Student t test was used for statistical analysis.
Results: Six treated animals showed no change in mean LV ejection fraction after 8 weeks (40.3% ± 0.9 [standard error of the mean] vs 41.0% ± 0.7) in contrast to a decrease measured in six control animals (41.4% ± 0.7 vs 36.1% ± 0.6, P < .001). AAV-VEGF improved wall thickening and circumferential strain in periinfarcted and remote myocardium. A greater reduction in gadoterate meglumine–enhanced infarct area was measured in treated animals (18.6% ± 1.5 of the LV mass at 3 days vs 9.8% ± 1.0 of the LV mass at 8 weeks, P < .001) compared with control animals (17.7% ± 2.0 vs 14.8% ± 1.0, P = .008). Findings at histopathologic evaluation indicated an increase in vascular density and a decrease in myocyte diameter in the periinfarcted myocardium of treated, compared with control, animals.
Conclusion: Angiogenesis and arteriogenesis induced by VEGF genes improved regional myocardial strain and wall thickening and preserved ejection fraction after infarction.
Radiology, 2007. 245(1): p. 196-205.
10.1148/radiol.2451061077.
http://radiology.rsna.org/content/245/1/196.full

Purpose: To define the relationship between left ventricular (LV) regional contractile function and the extent of myocardial scar in patients with chronic ischemic heart disease and multi-vessel coronary artery disease.
Methods: Twenty-three patients with chronic ischemic heart disease and 5 healthy volunteers underwent magnetic resonance imaging (MRI). In patients, the relative area (Percent Scar) and transmural extent (Transmurality) of myocardial infarction were computed from short-axis delayed enhancement images. In each image, myocardial segments were categorized based on the extent of infarction they contained, with 6 categories each for Percent Scar and Transmurality: normal, from healthy volunteers; and 0%; 1–25%, 26–50%, 51–75%, and > 76% from patients. In patients and volunteers, regional LV function was quantified by absolute systolic wall thickening from cine images and midwall circumferential strain using tagged images. Results. Compared to normal segments, regional LV function in patients was significantly diminished in all scar extent intervals, with wall thickening ≤ 1 mm and strain ≥ − 8% for all categories. Systolic wall thickening was reduced significantly in all categories above 50% Percent Scar and above 25% Transmurality in patients, relative to corresponding 0% categories. Circumferential strain was significantly reduced above 25% Percent Scar and above 25% Transmurality.
Conclusions: In patients with chronic ischemic heart disease and multi-vessel coronary artery disease, wall thickening was more sensitive to changes in scar Transmurality than to changes in Percent Scar. However, circumferential strain was equally sensitive to both indices. In general, circumferential strain was more sensitive than wall thickening to increases in scar extent.
Journal of Cardiovascular Magnetic Resonance, 2005. 7(3): p. 573 – 579.
http://informahealthcare.com/doi/abs/10.1081/JCMR-60652

Despite the numerous documented benefits of cardiac resynchronization therapy (CRT), a significant proportion of patients undergoing CRT do not demonstrate symptomatic or morphologic improvement, triggering the search to improve targeting of this therapy. Many studies now support direct assessment of mechanical dyssynchrony as a method to better identify CRT responders. Among the methods used, echo-Doppler imaging has taken center stage and is covered in other articles in this special issue; however, these methods have several inherent limitations, and other alternatives are also being explored such as magnetic resonance imaging (MRI). This review discusses the concepts and clinical use of MRI methods for quantitative assessment of mechanical dyssynchrony, highlighting newer acquisition and analysis methods and focusing on how the data can be synthesized into robust indexes of dyssynchronous heart failure.
Journal of the American College of Cardiology, 2005. 46(12): p. 2223-2228.
10.1016/j.jacc.2005.09.015.
http://content.onlinejacc.org/cgi/content/full/46/12/2223

Background: An elevated homocysteine (Hcy) level has been reported to be a risk factor for the development of congestive heart failure in individuals free of myocardial infarction. In this study, we aim to investigate the relationship between Hcy levels and regional left ventricular function in an asymptomatic population.
Method and Results: Regional peak systolic midwall circumferential strains were calculated from 1178 tagged magnetic resonance imaging studies in participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Left ventricular regions were defined by coronary territories (left anterior descending, left circumflex, right coronary artery). For the 1178 study participants (66±10 years of age, 58% males), the median (interquartile range) of Hcy was 9.1 (9.0 to 9.3). After adjustment for traditional risk factors, race, height, weight, left ventricular end-diastolic mass/volume, serum creatinine, and measures of atherosclerosis, reduced regional myocardial circumferential shortening across sex-specific quartiles of plasma Hcy in the left anterior descending (P=0.038) and left circumflex (P=0.009) regions persisted, which indicated an important association of reduced function with elevated Hcy. Multiple linear regression analyses confirmed that circumferential systolic dysfunction was associated with log transformed Hcy levels in the left anterior descending (P=0.004) and left circumflex (P=0.0002) regions. In the fully adjusted model, the odds ratio for left ventricular strains below the 10th percentile with 1 SD increases in log-transformed Hcy was 1.33 (95% confidence interval, 1.04 to 1.70; P=0.022) for the left anterior descending, 1.28 (95% confidence interval, 1.00 to 1.64; P=0.046) for the left circumflex, and 1.32 (95% confidence interval, 1.03 to 1.69; P=0.025) for the right coronary artery region.
Conclusion: In this asymptomatic population, an elevated Hcy level is associated with reduced regional left ventricular systolic function detected by tagged magnetic resonance imaging.
Circulation, 2007. 115(2): p. 180-187.
10.1161/CIRCULATIONAHA.106.633750.
http://circ.ahajournals.org/cgi/content/short/115/2/180

Objectives: We sought to examine the accuracy/consistency of a novel ultrasound speckle tracking imaging (STI) method for left ventricular torsion (LVtor) measurement in comparison with tagged magnetic resonance imaging (MRI) (a time-domain method similar to STI) and Doppler tissue imaging (DTI) (a velocity-based approach).
Background: Left ventricular torsion from helically oriented myofibers is a key parameter of cardiac performance but is difficult to measure. Ultrasound STI is potentially suitable for measurement of angular motion because of its angle-independence.
Methods: We acquired basal and apical short-axis left ventricular (LV) images in 15 patients to estimate LVtor by STI and compare it with tagged MRI and DTI. Left ventricular torsion was defined as the net difference of LV rotation at the basal and apical planes. For the STI analysis, we used high-frame (104 ± 12 frames/s) second harmonic two-dimensional images.
Results: Data on 13 of 15 patients were usable for STI analysis, and LVtor profile estimated by STI strongly correlated with those by tagged MRI (y = 0.95x + 0.19, r = 0.93, p < 0.0001, analyzed by repeated-measures regression models). The STI torsional velocity profile also correlated well with that by the DTI method (y = 0.79x + 2.4, r = 0.76, p < 0.0001, by repeated-measures regression models) with acceptable bias.
Conclusions: The STI estimation of LVtor is concordant with those analyzed by tagged MRI (data derived from tissue displacement) and also showed good agreement with those by DTI (data derived from tissue velocity). Ultrasound STI is a promising new method to assess LV torsional deformation and may make the assessment more available in clinical and research cardiology.
Journal of the American College of Cardiology, 2005. 45(12): p. 2034-2041.
10.1016/j.jacc.2005.02.082.
http://content.onlinejacc.org/cgi/content/full/45/12/2034

Background: Left ventricular (LV) torsional deformation is a sensitive index for LV performance but difficult to measure. The present study tested the accuracy of a novel method that uses Doppler tissue imaging (DTI) for quantifying LV torsion in humans with tagged magnetic resonance imaging (MRI) as a reference.
Methods and Results: Twenty patients underwent DTI and tagged MRI studies. Images of the LV were acquired at apical and basal short-axis levels to assess LV torsion. We calculated LV rotation by integrating the rotational velocity, determined from DTI velocities of the septal and lateral regions, and correcting for the LV radius over time. LV torsion was defined as the difference in LV rotation between the 2 levels. DTI rotational and torsional profiles throughout systole and diastole were compared with those by tagged MRI at isochronal points. Rotation and torsion by DTI were closely correlated with tagged MRI results during systole and early diastole (apical and basal rotation, r=0.87 and 0.90, respectively; for torsion, 0.84; P<0.0001, by repeated-measures regression models). Maximal torsion showed even better correlation (r=0.95, P<0.0001).
Conclusions: The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings
Circulation, 2005. 111(9): p. 1141-1147.
10.1161/01.CIR.0000157151.10971.98.
http://circ.ahajournals.org/cgi/content/full/111/9/1141

Objectives: The aim of the present study was to characterize the contraction pattern of the systemic right ventricle (RV).
Background: Reduced longitudinal function of the systemic RV compared with the normal RV has been interpreted as ventricular dysfunction. However, longitudinal shortening represents only one aspect of myocardial deformation, and changes in contraction in other dimensions have not previously been described.
Methods: Fourteen Senning-operated patients age 18.4 ± 0.9 years (mean ± SD) with transposition of the great arteries were studied. We compared the contraction pattern of the systemic RV with findings in the RV and left ventricle (LV) of normal subjects (n = 14) using tissue Doppler imaging and magnetic resonance imaging.
Results: In the systemic RV free wall, circumferential strain exceeded longitudinal strain (–23.3 ± 3.4% vs. –15.0 ± 3.0%, p < 0.001) as was also the case in the normal LV (–25.7 ± 3.1% vs. –16.5 ± 1.7%, p < 0.001), opposite from the findings in the normal RV (–15.8 ± 1.3% vs. –30.7 ± 3.3%, p < 0.001). Strain in the interventricular septum did not differ from normal. Ventricular torsion was essentially absent in the systemic RV (0.3 ± 1.8°), in contrast to a torsion of 16.7 ± 4.8° in the normal LV (p < 0.001).
Conclusions: In the systemic RV as in the normal LV, there was predominant circumferential over longitudinal free wall shortening, opposite from findings in the normal RV. This may represent an adaptive response to the systemic load. Noticeably, however, the systemic RV did not display torsion as found in the normal LV.
Journal of the American College of Cardiology, 2007. 49(25): p. 2450-6.
10.1016/j.jacc.2007.02.062.
http://content.onlinejacc.org/cgi/content/full/49/25/2450

This study examined left ventricular (LV) regional midwall circumferential strain by cardiac tagged magnetic resonance imaging in 32 long-term cocaine users and 14 nonusers. Most of the LV segmentations in the cocaine users had less average circumferential strain in the systolic and diastolic phases. The average diastolic strain in 5 ventricular segmentations was significantly less in the cocaine users (p<0.05).
In conclusion, long-term cocaine use may be associated with regional LV dysfunction, especially diastolic dysfunction.
The American Journal of Cardiology, 2006. 97(7): p. 1085-1088.
10.1016/j.amjcard.2005.10.056.
http://www.ajconline.org/article/S0002-9149(05)02236-8/abstract

Objectives: This study sought to investigate the relationship between C-reactive protein (CRP) and regional left ventricular (LV) function in asymptomatic individuals without a history of cardiovascular disease.
Background: C-reactive protein is associated with an increased risk for developing cardiovascular disease. However, the relationship between CRP and subclinical LV dysfunction has not been evaluated in asymptomatic individuals.
Methods: Regional myocardial function was analyzed as peak systolic circumferential shortening strain (Ecc) using the harmonic-phase method by tagged magnetic resonance imaging in 1,164 individuals without symptomatic cardiovascular disease from the MESA (Multi-Ethnic Study of Atherosclerosis) trial (age 66.4 ± 9.6 years old). Regions were defined by coronary territories: left anterior descending artery (LAD), left circumflex artery (LCX), and right coronary artery (RCA). The relationship between log-CRP concentration and Ecc was studied by multivariable linear regression after adjustment for demographic characteristics, risk factors, and therapy (including hormone replacement therapy).
Results: For each region, associations differed by gender with no association of CRP and regional LV function among women. In men, after adjustment, higher log-CRP was significantly associated with lower (absolute) Ecc in the LAD and RCA regions (regression coefficient 0.37 per unit higher log-CRP [95% confidence interval [CI] 0.08 to 0.65] and 0.31 [95% CI 0.02 to 0.59], respectively) and peak systolic Ecc overall (regression coefficient 0.32 [95% CI 0.05 to 0.58]). In the LCX region, the association was weaker (p = 0.06).
Conclusions: Among individuals without evident heart failure or other cardiovascular disorders, higher CRP was associated with lower systolic myocardial function in all regions in men but not in women. These findings support the role of inflammation and atherosclerosis in incipient myocardial dysfunction.
Journal of the American College of Cardiology, 2007. 49(5): p. 594-600.
10.1016/j.jacc.2006.09.040.
http://content.onlinejacc.org/cgi/content/full/49/5/594

Background: The transition from compensatory concentric remodeling to myocardial failure is not completely understood in humans. To investigate determinants of incipient myocardial dysfunction, we examined the association between concentric remodeling and regional LV function in asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA).
Methods and Results: Myocardial tagged MRI was performed. Regional myocardial function expressed as peak systolic midwall circumferential strain (Ecc) was analyzed in 441 consecutive studies by HARP (Harmonic Phase) tool. Peak Ecc was correlated with the extent of concentric remodeling determined by the ratio of left ventricular mass to end-diastolic volume (M/V ratio). In men, a gradual decline in peak global Ecc was seen with increasing M/V ratio (test for trend, P<0.001). Among women, however, Ecc tended to be lower only in the fifth compared with the first quintile of M/V ratio (P=0.1). The association of lower Ecc with increasing M/V ratio was regionally heterogeneous but was particularly prominent in the LAD region in men (test for trend, P<0.001) and in women (test for trend, P=0.02). In the right coronary and left circumflex artery territories, these associations were less marked in both genders.
Conclusions: In this cross-sectional study of asymptomatic individuals, concentric left ventricular remodeling was related to decreased regional systolic function. The reduction in regional function, which was more pronounced in the left anterior descending coronary artery territory, may reflect the local transition from compensatory remodeling to myocardial dysfunction.
Circulation, 2005. 112(7): p. 984-991.
10.1161/CIRCULATIONAHA.104.500488.
http://www.circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.104.500488v1

Background: Myocardial ischemia is an important determinant of regional left ventricular systolic function. Myocardial blood flow reserve may be impaired by cardiovascular disease before alterations of myocardial perfusion at rest become manifest. Nevertheless, the relation between flow reserve and regional myocardial function has not been studied in individuals without a history of clinical heart disease.
Methods and Results: Seventy-four participants (66±9 years, mean±SD) of the Multi-Ethnic Study of Atherosclerosis (MESA) underwent myocardial magnetic resonance tagging and contrast-enhanced perfusion studies. Regional myocardial function was evaluated as peak systolic circumferential strain (Ecc) in the three main coronary territories (left anterior descending [LAD], left circumflex, and right coronary artery [RCA]). Myocardial blood flow at rest and during adenosine-induced hyperemia was quantified by contrast-enhanced magnetic resonance imaging, to study the relation between regional flow and function after multivariable adjustment for age, gender, body mass index, left ventricular mass, and traditional risk factors. Lower regional myocardial blood flow during hyperemia was associated with reduced regional left ventricular function expressed as lower Ecc in the RCA (P<0.01) and left circumflex regions (P<0.05) measured in the subendocardium, mid-wall, and subepicardium. In contrast, no significant association was seen in the LAD territory (P=0.16). In addition, segmental function in LAD and RCA regions was reduced when individuals in the lowest 10th percentile for regional myocardial flow reserve were compared with the other participants. Absolute decreases in mid-wall Ecc LAD and RCA and global Ecc were 3.0%, 3.4%, and 2.8%, respectively (P<0.05 for all regions).
Conclusions: Lower myocardial flow reserve is related to reduced regional function in asymptomatic individuals.
Circulation, 2006. 114(4): p. 289-297.
10.1161/CIRCULATIONAHA.105.588525.
http://circ.ahajournals.org/cgi/content/short/114/4/289

Objectives: This study sought to test the hypothesis that reduced regional left ventricular (LV) function is associated with traditional risk factors including hypertension, hypercholesterolemia, and smoking in asymptomatic individuals.
Background: Coronary artery disease is the main etiology of congestive heart failure in the U.S. and Europe. However, the relationship between risk factors for coronary artery disease and decreased myocardial function has not been studied systematically in asymptomatic individuals.
Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) is a cohort study designed to investigate the nature of atherosclerosis in asymptomatic individuals. A total of 1,184 participants (45 to 84 years old) underwent tagged cardiac magnetic resonance imaging. Regional LV function was quantified by analyzing peak systolic circumferential strain (Ecc) in regions corresponding to the left anterior descending (LAD), circumflex (LCX), and right coronary (RCA) territories. The association between risk factors and strains was studied using multiple linear regression.
Results: Higher diastolic blood pressure (DBP) was associated with lower Ecc (p 0.002). The Ecc’s in the LAD territory of participants with DBP <80, 80 to 84, 85 to 89, and 90 mm Hg were –15.6%, –14.8%, –14.2%, and –13.7%, respectively (p < 0.001). Similar results were documented in other territories and after multivariable analysis. Smokers had lower Ecc in the LAD and RCA regions compared with nonsmokers. Furthermore, dose response relationship between cigarette consumption measured in pack-years and regional LV dysfunction by Ecc was noted (p 0.01 in LAD and RCA territories). Finally, combined diastolic hypertension and smoking was associated with a greater reduction of regional LV function.
Conclusions: Higher diastolic blood pressure and smoking are associated with decreased regional LV function in asymptomatic individuals.
Journal of the American College of Cardiology, 2006. 47(6): p. 1150-1158.
10.1016/j.jacc.2005.08.078.
http://content.onlinejacc.org/cgi/content/full/47/6/1150

Background: Cardiac dyssynchrony due to intraventricular conduction delay produces heterogeneous regional wall stress and worsens arrhythmia susceptibility in failing hearts. We examined whether chronic dyssynchrony per se induces regionally heterogeneous electrophysiological remodeling.
Methods and results: Adult dogs (n=9) underwent left bundle branch radiofrequency ablation (QRS duration increased from 50 ± 7 to 104 ± 7 ms); 6 untreated dogs served as controls. A subset of ablated (n=3) and control (n=4) dogs underwent tagged MR imaging to confirm ablation-induced left ventricular (LV) dyssynchrony. Four weeks later, hearts were excised and early (anterior)- and late (lateral)-activated myocardial segments were isolated. Conduction velocity (CV), action potential duration (APD), and refractory period (RP) of paced, arterially perfused myocardial wedges were studied by extracellular and optical mapping, and arrhythmia susceptibility was assessed by programmed stimulation. Regional stress-response kinase, calcium cycling, and gap junction protein expression were assayed by Western blotting, and the subcellular distribution of connexin43 was analyzed by immunofluorescence microscopy. CV, APD, and RP were significantly reduced in the late-activated, lateral wall of dyssynchronous hearts compared to the anterior wall. Normal differences in CV (endocardial>epicardial) were reversed in the dyssynchronous lateral LV. While the total expression of connexin43 was unaltered in dyssynchronous models, its subcellular location was redistributed in late-activated myocardium from intercalated discs to lateral myocyte membranes. Arrhythmias were rare in tissue from normal and dyssynchronous models. Total expression of calcium-cycling proteins (sarcoplasmic reticulum Ca2+-ATPase and phospholamban) and the stress-response kinase phospho-ERK did not vary regionally in either model.
Conclusions: Dyssynchrony even in the absence of LV dysfunction induces regionally specific changes in conduction and repolarization. These changes support a novel mechanism linking mechanical dyssynchrony to persistent electrophysiological remodeling and heterogeneity.
Cardiovascular Research, 2005. 67(1): p. 77-86.
10.1016/j.cardiores.2005.03.008.
http://cardiovascres.oxfordjournals.org/content/67/1/77.full

Background: Adenosine stress perfusion is very sensitive for detection of coronary artery disease (CAD), and yields good specificity. Standard adenosine cine imaging lacks high sensitivity, but is very specific. Myocardial tagging improves detection of wall motion abnormalities (WMAs). Perfusion and tagging cardiovascular magnetic resonance (CMR) both benefit from high field imaging (improved contrast to noise ratio and tag persistence). We investigated the diagnostic impact of a combined stress perfusion-tagging protocol for detection of CAD at 3 Tesla.
Methods: Stress perfusion and tagging images were acquired in 3 identical short axis locations (slice thickness 8 mm, FOV 320–380 mm, matrix 2562). A positive finding at coronary angiography was defined as stenosis or flow limiting restenosis > 50% in native and graft vessels. A true positive CMR – finding was defined as ≥ 1 perfusion deficit or new WMA during adenosine-stress in angiographically corresponding regions.
Results: We included 60 patients (males: 41, females: 19; 21 suspected, 39 known CAD). Myocardial tagging extended stress imaging by 1.5–3 min and was well tolerated by all patients. Sensitivity and specificity for detection of significant CAD by adenosine stress perfusion were 0.93 and 0.84, respectively. The sensitivity of adenosine stress tagging was less (0.64), while the specificity was very high (1.0). The combination of both stress perfusion and stress tagging did not increase sensitivity.
Conclusion: The combined adenosine stress perfusion-tagging protocol delivers high sensitivity and specificity for detection of significant CAD. While the sensitivity of adenosine stress tagging is poor compared to perfusion imaging, its specificity is very high. This technique should thus prove useful in cases of inconclusive perfusion studies to help avoid false positive results.
Journal of Magnetic Resonance Imaging, 2006. 23(4): p. 477-480.
10.1186/1532-429X-10-59.
http://jcmr-online.com/content/10/1/59